Crystallins are the major components of the normal eye lens. In a novel evolutionary process crystallins have arisen by the gene recruitment of stress-proteins and enzymes without prior gene duplication. In the lens- specific alternative promoter of guinea pig NADPH:quinone oxidoreductase/zeta-crystallin we have identified an element that is essent l for function. We now find that this element contains a binding site for Pa 6, a "master gene" for eye development. Mutation of the Pax-6 site abolishes promoter function and Pax-6 is required for formation a lens- specific complex. Futhermore, Pax-6 is expressed in the mature lens. Pax- thus, has a continuing role in maintenance of lens-specific gene expression and a key role in the gene recruitment of a crystallin. mu-crystallin, whi was discovered in marsupial lenses, is a novel NADPH-binding protein relate to enzymes of ornithine and glutamate metabolism. In humans, in which it has not been recruited as a crystallin, it is expressed most abundantly in photoreceptor outer segments, suggesting an unexpected role in the visual process. Other proteins are essential for normal development in lens. MIF, a small protein expressed in differentiating lens cells, is essential for progression through the cycle. Antisense to MIF abolishes proliferation of growth factor stimulated and cancer cells and halts them at the G1/S boundary. Promoter analysis of the human MIF gene has identified a region required for growth factor response. We have also found that LP2, a lipid/retinoid binding protein we have cloned from bovine lens, is expresse preferentially in differentiated fiber cells.